Generally, bee venom refers to a toxin possessed by bees, which is known to aid in the alleviation of arthritis, arteriosclerosis, and lower back pains; and is also effectively used in the treatment of skin wounds, improvement of the immune system via antibacterial and anti-inflammatory responses, cosmetic treatments such as skin whitening and wrinkle improvement, etc.
Purified bee venom (PBV) is a product obtained from bee venom collected from bees using a bee venom collector after the bee venom goes through a series of processes including natural drying, purification, sterilization and lyophilization, etc. The PBV and raw bee venom are known to have similar physiological activities.
The constitutional components of a PBV with physiological activities are shown in Table 1 below.
TABLE 1ComponentsPharmacological ActionsPeptidesmelittincell lysis, anti-inflammation,immune responseapaminNeuralgia relief, pain relief,anti-inflammation, immune responseMCD-peptide 401anti-inflammationadolapinanti-inflammation, pain relief,antipyretic actionproteaseinhibition of lysis of proteins andinhibitoresters, anti-inflammationsecapinsedating hypothermiatertiapindegranulation of mast cellsprocamine A, Bradiation protection-related actionProteinshyaluronidasehistologic reaction,(Enzyme)antigenic componentphospholipase A2destruction of cell structure,hemolysis, catalytic actionα-glucosidasepromotion of antibody functionphosphotasepromotion of antibody functionlysophospholipaseinhibition of phospholipase A2activityAmineshistaminehypotensive action,intestinal contraction,promotion of gastric acid releasedopamineneurotransmitter
The PBV consists of more than 40 different kinds of components including peptides, proteins (e.g., enzymes), low molecular active amines, etc. As shown in Table 1, the active ingredients of the PBV are peptides (apamin, melittin, and MCD), active amines (histamine and dopamin), amino acids, etc., all having a molecular weight of 11 kDa (kilo-dalton) or less.
Among the various bee venom components, a protein component includes phospholipase A2 with a molecular weight of 13 kDa or higher, hyaluronidase, phosphatase, α-glucosidase, etc., which are mainly involved in physiological activities such as destruction of blood cell membranes, blood coagulation, vasodilation and vasopermeability, promotion of blood circulation and protein hydrolysis.
In particular, phospholipase A2 and hyaluronidase are bee venom components that can induce strong allergic reactions which may cause serious safety issues in some people having hypersensitivity thereto (Stefan Bogdanov; Bee Venom: composition, Health, Medicine: A Review, Bee Product Science (2011)).
Due to the adverse effects of the bee venom as described above, its efficient dose is limited, which again limits its physiological effects, thus preventing its intrinsic effects from being exhibited.
Korean Patent Application Publication No. 10-2012-0003178 relates to a composition with skin lightening and moisturizing effects containing bee venom extracts as active ingredients, and describes a composition or a cosmetic composition with skin lightening and moisturizing effects containing pretreated bee venom or bee venom extracts.
However, the related arts as in the above method fail to include a step to remove phospholipase A2 and hyaluronidase, which are strong inducers of allergic reactions. Accordingly, the use of the composition or cosmetic composition containing the bee venom extracts, manufactured according to the conventional method, as active ingredients by a person hypersensitive to bee venom may cause very serious safety issues.
Additionally, a method to add an inhibitor to prevent allergic reactions has been suggested but it was proven not advantageous because it could not completely solve the allergy issue and adverse reactions may occur due to the allergic reaction inhibitor.
Additionally, a method to remove phospholipase A2 and hyaluronidase via high performance liquid chromatography (HPLC) or gel filtration has also been suggested but they too were not advantageous because of the drastic decrease in yield during the isolation or purification process and difficulty in the large-scale production of the same.